State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China.
National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Clin Mol Hepatol. 2024 Oct;30(4):620-648. doi: 10.3350/cmh.2024.0315. Epub 2024 Jul 11.
Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.
脂肪性肝病是全世界肝硬化和终末期肝癌的主要病因，影响了近全球四分之一的人口。脂肪性肝病包括代谢相关脂肪性肝病（MetALD）和代谢相关脂肪性肝损伤（MASLD），可导致无症状性肝脂肪变性、纤维化、肝硬化及相关并发症。免疫过程包括肠道菌群失调、脂肪-肝脏器官串扰、肝细胞死亡和免疫细胞介导的炎症过程。值得注意的是，各种免疫细胞，如 B 细胞、浆细胞、树突状细胞、常规 CD4+和 CD8+T 细胞、固有样 T 细胞、血小板、中性粒细胞和巨噬细胞，在 MetALD 和 MASLD 的发生发展中发挥着重要作用。针对肝细胞死亡、炎症反应和肠道微生物组的免疫调节包括 N-乙酰半胱氨酸、selonsertib、F-652、泼尼松、己酮可可碱、阿那白滞素、JKB-121、HA35、奥贝胆酸、益生菌、益生元、抗生素和粪便微生物群移植。了解脂肪性肝病的免疫机制对于推进临床治疗策略至关重要。
